Publications by authors named "Atsushi Miyawaki"

301 Publications

Association of managerial position with cardiovascular risk factors: A fixed-effects analysis for Japanese employees.

Scand J Work Environ Health 2021 May 19. Epub 2021 May 19.

Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.

Objectives Although higher occupational classes have been reported to be associated with better health, researchers do not fully understand whether such associations derive from the position or individual characteristics of the person in that position. We examined the association between being a manager and cardiovascular disease (CVD) risk factors using unique panel data in Japan that annually observed employees' occupational class and health conditions. Methods We analyzed data for 45 888 observations from a Japanese company from 2013 through 2017. The association between being a manager and CVD risk factors (metabolic risks and health-related behaviors) were evaluated using simple pooled cross-sectional analyses with adjustment for age, sex, marital status, and overtime-working hours. We further incorporated employee-level fixed-effects into the models to examine whether the associations were subject to individual time-invariant factors. Results The pooled cross-sectional analyses showed that, compared to non-managers, managers had 2.0 mg/dl lower low density lipoprotein cholesterol (LDL-C) level, 1.4 mmHg-lower systolic blood pressure, and 0.2 kg/m lower body mass index (BMI). After adjusting for employee-level fixed-effects, being a manager was associated with a significantly 2.2 mg/dl higher LDL-C level. However, the associations between an individual's management status and blood pressure or BMI were not significant. Furthermore, managers were 5.5% less likely to exercise regularly and 6.1% less likely to report sufficient sleep in the fixed-effects models, although the pooled cross-sectional analyses did not demonstrate these significant associations. Conclusions Our findings suggest the necessity of considering these unfavorable health risks associated with being promoted to a manager.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5271/sjweh.3966DOI Listing
May 2021

A unique mode of keratinocyte death requires intracellular acidification.

Proc Natl Acad Sci U S A 2021 Apr;118(17)

Laboratory for Skin Homeostasis, RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan;

The stratum corneum (SC), the outermost epidermal layer, consists of nonviable anuclear keratinocytes, called corneocytes, which function as a protective barrier. The exact modes of cell death executed by keratinocytes of the upper stratum granulosum (SG1 cells) remain largely unknown. Here, using intravital imaging combined with intracellular Ca- and pH-responsive fluorescent probes, we aimed to dissect the SG1 death process in vivo. We found that SG1 cell death was preceded by prolonged (∼60 min) Ca elevation and rapid induction of intracellular acidification. Once such intracellular ionic changes were initiated, they became sustained, irreversibly committing the SG1 cells to corneocyte conversion. Time-lapse imaging of isolated murine SG1 cells revealed that intracellular acidification was essential for the degradation of keratohyalin granules and nuclear DNA, phenomena specific to SC corneocyte formation. Furthermore, intravital imaging showed that the number of SG1 cells exhibiting Ca elevation and the timing of intracellular acidification were both tightly regulated by the transient receptor potential cation channel V3. The functional activity of this protein was confirmed in isolated SG1 cells using whole-cell patch-clamp analysis. These findings provide a theoretical framework for improved understanding of the unique molecular mechanisms underlying keratinocyte-specific death mode, namely corneoptosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1073/pnas.2020722118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8092583PMC
April 2021

Comparison of Childbirth Delivery Outcomes and Costs of Care Between Women Experiencing vs Not Experiencing Homelessness.

JAMA Netw Open 2021 Apr 1;4(4):e217491. Epub 2021 Apr 1.

Department of Health Policy and Management, University of California, Los Angeles Fielding School of Public Health.

Importance: Women and families constitute the fastest-growing segments of the homeless population. However, there is limited evidence on whether women experiencing homelessness have poorer childbirth delivery outcomes and higher costs of care compared with women not experiencing homelessness.

Objective: To compare childbirth delivery outcomes and costs of care between pregnant women experiencing homelessness vs those not experiencing homelessness.

Design, Setting, And Participants: This cross-sectional study included 15 029 pregnant women experiencing homelessness and 308 242 pregnant women not experiencing homelessness who had a delivery hospitalization in 2014. The study used statewide databases that included all hospital admissions in 3 states (ie, Florida, Massachusetts, and New York). Delivery outcomes and delivery-associated costs were compared between pregnant women experiencing homelessness and those not experiencing homelessness cared for at the same hospital (analyzed using the overlap propensity-score weighting method and multivariable regression models with hospital fixed effects). The Benjamini-Hochberg false discovery rate procedure was used to account for multiple comparisons. Data were analyzed from January 2020 through May 2020.

Exposure: Housing status at delivery hospitalization.

Main Outcomes And Measures: Outcome variables included obstetric complications (ie, antepartum hemorrhage, placental abnormalities, premature rupture of the membranes, preterm labor, and postpartum hemorrhage), neonatal complications (ie, fetal distress, fetal growth restriction, and stillbirth), delivery method (ie, cesarean delivery), and delivery-associated costs.

Results: Among 15 029 pregnant women experiencing homelessness (mean [SD] age, 28.5 [5.9] years) compared with 308 242 pregnant women not experiencing homelessness (mean [SD] age, 29.4 [5.8] years) within the same hospital, those experiencing homelessness were more likely to experience preterm labor (adjusted probability, 10.5% vs 6.7%; adjusted risk difference [aRD], 3.8%; 95% CI, 1.2%-6.5%; adjusted P = .03) and had higher delivery-associated costs (adjusted costs, $6306 vs $5888; aRD, $417; 95% CI, $156-$680; adjusted P = .02) compared with women not experiencing homelessness. Those experiencing homelessness also had a higher probability of placental abnormalities (adjusted probability, 4.0% vs 2.0%; aRD, 1.9%; 95% CI, 0.4%-3.5%; adjusted P = .053), although this difference was not statistically significant.

Conclusions And Relevance: This study found that women experiencing homelessness, compared with those not experiencing homelessness, who had a delivery and were admitted to the same hospital were more likely to experience preterm labor and incurred higher delivery-associated costs. These findings suggest wide disparities in delivery-associated outcomes between women experiencing homelessness and those not experiencing homelessness in the US. The findings highlight the importance for health care professionals to actively screen pregnant women for homelessness during prenatal care visits and coordinate their care with community health programs and social housing programs to make sure their health care needs are met.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamanetworkopen.2021.7491DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8063065PMC
April 2021

Fast, cell-resolution, contiguous-wide two-photon imaging to reveal functional network architectures across multi-modal cortical areas.

Neuron 2021 Jun 19;109(11):1810-1824.e9. Epub 2021 Apr 19.

Center for Brain Science, RIKEN, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan. Electronic address:

Fast and wide field-of-view imaging with single-cell resolution, high signal-to-noise ratio, and no optical aberrations have the potential to inspire new avenues of investigations in biology. However, such imaging is challenging because of the inevitable tradeoffs among these parameters. Here, we overcome these tradeoffs by combining a resonant scanning system, a large objective with low magnification and high numerical aperture, and highly sensitive large-aperture photodetectors. The result is a practically aberration-free, fast-scanning high optical invariant two-photon microscopy (FASHIO-2PM) that enables calcium imaging from a large network composed of ∼16,000 neurons at 7.5 Hz from a 9 mm contiguous image plane, including more than 10 sensory-motor and higher-order areas of the cerebral cortex in awake mice. Network analysis based on single-cell activities revealed that the brain exhibits small-world rather than scale-free behavior. The FASHIO-2PM is expected to enable studies on biological dynamics by simultaneously monitoring macroscopic activities and their compositional elements.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neuron.2021.03.032DOI Listing
June 2021

Association between participation in the government subsidy programme for domestic travel and symptoms indicative of COVID-19 infection in Japan: cross-sectional study.

BMJ Open 2021 04 13;11(4):e049069. Epub 2021 Apr 13.

Division of General Internal Medicine and Health Services Research, UCLA David Geffen School of Medicine, Los Angeles, California, USA.

Objective: To investigate the association between participation in government subsidies for domestic travel (subsidise up to 50% of all travel expenses) introduced nationally in Japan on 22 July 2020 and the incidence of symptoms indicative of COVID-19 infections.

Design: Cross-sectional analysis of nationally representative survey data.

Setting: Internet survey conducted between 25 August and 30 September 2020 in Japan. Sampling weights were used to calculate national estimates.

Participants: 25 482 survey respondents (50.3% (12 809) women; mean (SD) age, 48.8 (17.4) years).

Main Outcome Measures: Incidence rate of five symptoms indicative of the COVID-19 infection (high fever, sore throat, cough, headache, and smell and taste disorder) within the past month of the survey, after adjustment for characteristics of individuals and prefecture fixed effects (effectively comparing individuals living in the same prefecture).

Results: At the time of the survey, 3289 (12.9%) participated in the subsidy programme. After adjusting for potential confounders, we found that participants in the subsidy programme exhibited higher incidence of high fever (adjusted rate, 4.7% for participants vs 3.7% for non-participants; adjusted OR (aOR) 1.83; 95% CI 1.34 to 2.48; p<0.001), sore throat (19.8% vs 11.3%; aOR 2.09; 95% CI 1.37 to 3.19; p=0.002), cough (19.0% vs 11.3%; aOR 1.96; 95% CI 1.26 to 3.01; p=0.008), headache (29.2% vs 25.5%; aOR 1.24; 95% CI 1.08 to 1.44; p=0.006) and smell and taste disorder (2.6% vs 1.8%; aOR 1.98; 95% CI 1.15 to 3.40; p=0.01) compared with non-participants. These findings remained qualitatively unaffected by additional adjustment for the use of 17 preventative measures (eg, social distancing, wearing masks and handwashing) and fear against the COVID-19 infection.

Conclusions: The participation of the government subsidy programme for domestic travel was associated with a higher probability of exhibiting symptoms indicative of the COVID-19 infection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjopen-2021-049069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8050877PMC
April 2021

Trajectories of Long-Term Care Expenditure During the Last 5 Years of Life in Japan: A Nationwide Retrospective Cohort Study.

J Am Med Dir Assoc 2021 Mar 5. Epub 2021 Mar 5.

Faculty of Medicine, Department of Health Services Research, University of Tsukuba, Ibaraki, Japan; Health Services Research & Development Center, University of Tsukuba, Tsukuba, Ibaraki, Japan.

Objectives: Despite the significant utilization of long-term care (LTC) services at the end of life, evidence on the trajectory of LTC expenditure in later life is scarce. This study aims to identify distinct trajectories of LTC expenditure in the last 5 years of life and to examine whether these trajectories differ according to cause of death.

Design: A nationwide retrospective longitudinal cohort study based on linked data of National LTC Claims and the Japan's National Vital Statistic.

Setting And Participants: Participants comprised decedents aged 70 years or older and who died in 2017.

Methods: We assessed 5 years of monthly LTC expenditure among participants and applied group-based trajectory model to identify distinct trajectories of LTC expenditure. Subsequently multinominal logistic regression analysis was performed to investigate how these trajectories vary according to cause of death.

Results: Among 1,124,335 decedents, 4 distinct trajectories of LTC expenditure were identified: persistently low (58.5%), late increase (9.8%), progressive increase then late decrease (8.8%), and persistently high (22.9%). Approximately 80.7% of total LTC expenditure was spent by the persistently high group. After adjustment for age and sex; deaths due to age-related physical debility and dementia were associated with persistently high LTC expenditure.

Conclusions And Implications: Ongoing discussions of LTC policy and reducing LTC expenditure may be more effective when emphasizing persistently high spenders. In addition, budget allocation for LTC at the end of life should be combined with data for health conditions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jamda.2021.01.084DOI Listing
March 2021

Relationships between social spending and childhood obesity in OECD countries: an ecological study.

BMJ Open 2021 02 23;11(2):e044205. Epub 2021 Feb 23.

Department of Public Health, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.

Objectives: The burden of childhood obesity is clustered among children in low-socioeconomic groups. Social spending on children-public welfare expenditure on families and education-may curb childhood obesity by reducing socioeconomic disadvantages. The objective of this study was to examine the relationship between social spending on children and childhood obesity across the Organisation for Economic Cooperation and Development (OECD) countries.

Design: Ecological study.

Setting: Data on social spending on children were obtained from the OECD Social Expenditure Database and the OECD educational finance indicators dataset during 2000-2015. Data on childhood obesity were obtained from the NCD Risk Factor Collaboration database.

Participants: Aggregated statistics on obesity among children aged 5-19 years, estimated for OECD 35 countries based on the measured height and weight on 31.5 million children.

Outcome Measures: Country-level prevalence of obesity among children aged 5-19 years.

Results: In cross-sectional analyses in 2015, social spending on children was inversely associated with the prevalence of childhood obesity after adjusting for potential confounders (the gross domestic product per capita, unemployment rate, poverty rate, percentage of children aged <20 years and prevalence of childhood obesity in 2000). In addition, when we focused on changes from 2000 to 2015, an average annual increase of US$100 in social spending per child was associated with a decrease in childhood obesity by 0.6 percentage points for girls (p=0.007) and 0.7 percentage points for boys (p=0.04) between 2000 and 2015, after adjusting for the potential confounders. The dimensions of social spending that contributed to these associations between the changes in social spending on children and childhood obesity were early childhood education and care (ECEC) and school education for girls and ECEC for boys.

Conclusion: Countries that increase social spending on children tend to experience smaller increases in childhood obesity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjopen-2020-044205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7907862PMC
February 2021

Gravity sensing in plant and animal cells.

NPJ Microgravity 2021 Feb 8;7(1). Epub 2021 Feb 8.

Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.

Gravity determines shape of body tissue and affects the functions of life, both in plants and animals. The cellular response to gravity is an active process of mechanotransduction. Although plants and animals share some common mechanisms of gravity sensing in spite of their distant phylogenetic origin, each species has its own mechanism to sense and respond to gravity. In this review, we discuss current understanding regarding the mechanisms of cellular gravity sensing in plants and animals. Understanding gravisensing also contributes to life on Earth, e.g., understanding osteoporosis and muscle atrophy. Furthermore, in the current age of Mars exploration, understanding cellular responses to gravity will form the foundation of living in space.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41526-020-00130-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870899PMC
February 2021

DHODH inhibition synergizes with DNA-demethylating agents in the treatment of myelodysplastic syndromes.

Blood Adv 2021 01;5(2):438-450

Division of Stem Cell and Molecular Medicine, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.

Dihydroorotate dehydrogenase (DHODH) catalyzes a rate-limiting step in de novo pyrimidine nucleotide synthesis. DHODH inhibition has recently been recognized as a potential new approach for treating acute myeloid leukemia (AML) by inducing differentiation. We investigated the efficacy of PTC299, a novel DHODH inhibitor, for myelodysplastic syndrome (MDS). PTC299 inhibited the proliferation of MDS cell lines, and this was rescued by exogenous uridine, which bypasses de novo pyrimidine synthesis. In contrast to AML cells, PTC299 was inefficient at inhibiting growth and inducing the differentiation of MDS cells, but synergized with hypomethylating agents, such as decitabine, to inhibit the growth of MDS cells. This synergistic effect was confirmed in primary MDS samples. As a single agent, PTC299 prolonged the survival of mice in xenograft models using MDS cell lines, and was more potent in combination with decitabine. Mechanistically, a treatment with PTC299 induced intra-S-phase arrest followed by apoptotic cell death. Of interest, PTC299 enhanced the incorporation of decitabine, an analog of cytidine, into DNA by inhibiting pyrimidine production, thereby enhancing the cytotoxic effects of decitabine. RNA-seq data revealed the marked downregulation of MYC target gene sets with PTC299 exposure. Transfection of MDS cell lines with MYC largely attenuated the growth inhibitory effects of PTC299, suggesting MYC as one of the major targets of PTC299. Our results indicate that the DHODH inhibitor PTC299 suppresses the growth of MDS cells and acts in a synergistic manner with decitabine. This combination therapy may be a new therapeutic option for the treatment of MDS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/bloodadvances.2020001461DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7839369PMC
January 2021

Trends in Diabetes Care during the COVID-19 Outbreak in Japan: an Observational Study.

J Gen Intern Med 2021 05 19;36(5):1460-1462. Epub 2021 Jan 19.

Department of Public Health, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11606-020-06413-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7814982PMC
May 2021

Casting Light on Life.

Authors:
Atsushi Miyawaki

Keio J Med 2020 ;69(4):105

RIKEN Center for Brain Science, Saitama, Japan.

The behavior of biochemical molecules moving around in cells makes me think of a school of whales wandering in the ocean, captured by the Argus system on the artificial satellite. When bringing a whale back into the sea --- with a transmitter on its dorsal fin, every staff member hopes that it will return safely to a school of its species. A transmitter is now minute in size, but it was not this way before. There used to be some concern that a whale fitted with a transmitter could be given the cold shoulder and thus ostracized by other whales for "wearing something annoying." How is whale's wandering related to the tide or a shoal of small fish? What kind of interaction is there among different species of whales? We human beings have attempted to fully understand this fellow creature in the sea both during and since the age of whale fishing.In a live cell imaging experiment, a luminescent probe replaces a transmitter. We put a luminescent probe on a specific region of a biological molecule and bring it back into a cell. We can then visualize how the molecule behaves in response to external stimulation. Since luminescence is a physical phenomenon, we can extract various kinds of information by making full use of its characteristics.Cruising inside cells in a supermicro corps, gliding down in a microtubule like a roller coaster, pushing our ways through a jungle of chromatin while hoisting a flag of nuclear localization signal --- we are reminded to retain a playful and adventurous perspective at all times. What matters is mobilizing all capabilities of science and giving full play to our imagination. We believe that such serendipitous findings can arise out of such a sportive mind, a frame of mind that prevails when enjoying whale-watching.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2302/kjm.69-001-ABSTDOI Listing
January 2020

Association between Participation in Government Subsidy Program for Domestic Travel and Symptoms Indicative of COVID-19 Infection.

medRxiv 2020 Dec 5. Epub 2020 Dec 5.

Importance: As countermeasures against the economic downturn caused by the coronavirus 2019 (COVID-19) pandemic, many countries have introduced or considering financial incentives for people to engage in economic activities such as travel and use restaurants. Japan has implemented a large-scale, nationwide government-funded program that subsidizes up to 50% of all travel expenses since July 2020 with the aim of reviving the travel industry. However, it remains unknown as to how such provision of government subsidies for travel impacted the COVID-19 pandemic.

Objective: To investigate the association between participation in government subsidies for domestic travel in Japan and the incidence of COVID-19 infections.

Design Setting And Participants: Using the data from a large internet survey conducted between August 25 and September 30, 2020, in Japan, we examined whether individuals who used subsidies experienced a higher likelihood of symptoms indicative of the COVID-19 infection.

Exposure: Participation in the government subsidy program for domestic travel.

Main Outcomes And Measures: Five symptoms indicative of the COVID-19 infection (high fever, throat pain, cough, headache, and smell and taste disorder) within the past one month of the survey.

Results: Of the 25,482 respondents (50.3% [12,809] women; mean [SD] age, 48.4 [17.4] years), 3,289 (12.9%) participated in the subsidy program at the time of survey. After adjusting for potential confounders, we found that the participants of the subsidy program exhibited higher incidence of high fever (adjusted rate, 4.8% for participants vs. 3.7% for non-participants; adjusted odds ratio [aOR], 1.90; 95%CI, 1.40-2.56; p<0.001), throat pain (20.0% vs. 11.3%; aOR, 2.13; 95%CI, 1.39-3.26; p=0.002), cough (19.2% vs. 11.2%; aOR 1.97; 95%CI, 1.28-3.03; p=0.004), headache (29.4% vs. 25.5%; aOR, 1.26; 95%CI, 1.09-1.46; p=0.005), and smell and taste disorder (2.6% vs. 1.7%; aOR 2.01; 95%CI; 1.16-3.49; p=0.01) compared with the non-participants.

Conclusion And Relevance: The participants of government subsidies for domestic travel experienced a higher incidence of symptoms indicative of the COVID-19 infection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1101/2020.12.03.20243352DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724675PMC
December 2020

Trends in intensive neonatal care during the COVID-19 outbreak in Japan.

Arch Dis Child Fetal Neonatal Ed 2021 May 23;106(3):327-329. Epub 2020 Nov 23.

Department of Public Health, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Japan

The reduction in the use of neonatal intensive care units (NICUs) during the COVID-19 outbreak has been reported, but whether this phenomenon is widespread across countries is unclear. Using a large-scale inpatient database in Japan, we analysed the intensive neonatal care volume and the number of preterm births for weeks 10-17 vs weeks 2-9 (during and before the outbreak) of 2020 with adjustment for the trends during the same period of 2019. We found statistically significant reductions in the numbers of NICU admissions (adjusted incidence rate ratio (aIRR), 0.76; 95% CI, 0.65 to 0.89) and neonatal resuscitations (aIRR, 0.37; 95% CI, 0.25 to 0.55) during the COVID-19 outbreak. Along with the decrease in the intensive neonatal care volume, preterm births before 34 gestational weeks (aIRR, 0.71) and between 34 0/7 and 36 6/7 gestational weeks (aIRR, 0.85) also showed a significant reduction. Further studies about the mechanism of this phenomenon are warranted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/archdischild-2020-320521DOI Listing
May 2021

Trends in hospitalizations for asthma during the COVID-19 outbreak in Japan.

J Allergy Clin Immunol Pract 2021 01 14;9(1):494-496.e1. Epub 2020 Oct 14.

Department of Public Health, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaip.2020.09.060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7553873PMC
January 2021

Efficacy of the novel tubulin polymerization inhibitor PTC-028 for myelodysplastic syndrome.

Cancer Sci 2020 Dec 2;111(12):4336-4347. Epub 2020 Nov 2.

Division of Stem Cell and Molecular Medicine, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.

Monomer tubulin polymerize into microtubules, which are highly dynamic and play a critical role in mitosis. Therefore, microtubule dynamics are an important target for anticancer drugs. The inhibition of tubulin polymerization or depolymerization was previously targeted and exhibited efficacy against solid tumors. The novel small molecule PTC596 directly binds tubulin, inhibits microtubule polymerization, downregulates MCL-1, and induces p53-independent apoptosis in acute myeloid leukemia cells. We herein investigated the efficacy of PTC-028, a structural analog of PTC596, for myelodysplastic syndrome (MDS). PTC-028 suppressed growth and induced apoptosis in MDS cell lines. The efficacy of PTC028 in primary MDS samples was confirmed using cell proliferation assays. PTC-028 synergized with hypomethylating agents, such as decitabine and azacitidine, to inhibit growth and induce apoptosis in MDS cells. Mechanistically, a treatment with PTC-028 induced G2/M arrest followed by apoptotic cell death. We also assessed the efficacy of PTC-028 in a xenograft mouse model of MDS using the MDS cell line, MDS-L, and the AkaBLI bioluminescence imaging system, which is composed of AkaLumine-HCl and Akaluc. PTC-028 prolonged the survival of mice in xenograft models. The present results suggest a chemotherapeutic strategy for MDS through the disruption of microtubule dynamics in combination with DNA hypomethylating agents.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/cas.14684DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7734154PMC
December 2020

A hypothalamic novelty signal modulates hippocampal memory.

Nature 2020 10 30;586(7828):270-274. Epub 2020 Sep 30.

Laboratory for Circuit and Behavioral Physiology, RIKEN Center for Brain Science, Wakoshi, Japan.

The ability to recognize information that is incongruous with previous experience is critical for survival. Novelty signals have therefore evolved in the mammalian brain to enhance attention, perception and memory. Although the importance of regions such as the ventral tegmental area and locus coeruleus in broadly signalling novelty is well-established, these diffuse monoaminergic transmitters have yet to be shown to convey specific information on the type of stimuli that drive them. Whether distinct types of novelty, such as contextual and social novelty, are differently processed and routed in the brain is unknown. Here we identify the supramammillary nucleus (SuM) as a novelty hub in the hypothalamus. The SuM region is unique in that it not only responds broadly to novel stimuli, but also segregates and selectively routes different types of information to discrete cortical targets-the dentate gyrus and CA2 fields of the hippocampus-for the modulation of mnemonic processing. Using a new transgenic mouse line, SuM-Cre, we found that SuM neurons that project to the dentate gyrus are activated by contextual novelty, whereas the SuM-CA2 circuit is preferentially activated by novel social encounters. Circuit-based manipulation showed that divergent novelty channelling in these projections modifies hippocampal contextual or social memory. This content-specific routing of novelty signals represents a previously unknown mechanism that enables the hypothalamus to flexibly modulate select components of cognition.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41586-020-2771-1DOI Listing
October 2020

On-Site Monitoring of Postoperative Bile Leakage Using Bilirubin-Inducible Fluorescent Protein.

World J Surg 2020 Dec 9;44(12):4245-4253. Epub 2020 Sep 9.

Hepatobiliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo, 113-8655, Japan.

Background: Bile leakage is the most common postoperative complication associated with hepatobiliary and pancreatic surgery. Until now, however, a rapid, accurate diagnostic method for monitoring intraoperative and postoperative bile leakage had not been established.

Method: Bilirubin levels in drained abdominal fluids collected from 23 patients who had undergone hepatectomy (n = 22) or liver transplantation (n = 1) were measured using a microplate reader with excitation/emission wavelengths of 497/527 nm after applying 5 µM of UnaG to the samples. UnaG was also sprayed directly on hepatic raw surfaces in swine hepatectomy models to identify bile leaks by fluorescence imaging.

Results: The bilirubin levels measured by UnaG fluorescence imaging showed favorable correlations with the results of the conventional light-absorptiometric methods (indirect bilirubin: rs = 0.939, p < 0.001; direct bilirubin: rs = 0.929, p < 0.001). Approximate time required for bilirubin measurements with UnaG was 15 min, whereas it took about 40 min with the conventional method at a hospital laboratory. Following administration of UnaG on hepatic surfaces, the fluorescence imaging identified bile leaks not only on the resected specimens but also in the abdominal cavity of the swine hepatectomy models.

Conclusion: Fluorescence imaging techniques using UnaG may enable real-time identification of bile leaks during hepatectomy and on-site rapid diagnosis of bile leaks after surgery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00268-020-05774-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7599156PMC
December 2020

Diffusible GRAPHIC to visualize morphology of cells after specific cell-cell contact.

Sci Rep 2020 09 2;10(1):14437. Epub 2020 Sep 2.

Molecular Mechanisms of Brain Development, Center for Brain Science (CBS), RIKEN, Saitama, Japan.

The ability to identify specific cell-cell contact in the highly heterogeneous mammalian body is crucial to revealing precise control of the body plan and correct function. To visualize local connections, we previously developed a genetically encoded fluorescent indicator, GRAPHIC, which labels cell-cell contacts by restricting the reconstituted green fluorescent protein (GFP) signal to the contact site. Here, we modify GRAPHIC to give the reconstituted GFP motility within the membrane, to detect cells that make contact with other specific cells. Removal of leucine zipper domains, located between the split GFP fragment and glycophosphatidylinositol anchor domain, allowed GFP reconstituted at the contact site to diffuse throughout the entire plasma membrane, revealing cell morphology. Further, depending on the structural spacers employed, the reconstituted GFP could be selectively targeted to N terminal (NT)- or C terminal (CT)-probe-expressing cells. Using these novel constructs, we demonstrated that we can specifically label NT-probe-expressing cells that made contact with CT-probe-expressing cells in an epithelial cell culture and in Xenopus 8-cell-stage blastomeres. Moreover, we showed that diffusible GRAPHIC (dGRAPHIC) can be used in neuronal circuits to trace neurons that make contact to reveal a connection map. Finally, application in the developing brain demonstrated that the dGRAPHIC signal remained on neurons that had transient contacts during circuit development to reveal the contact history. Altogether, dGRAPHIC is a unique probe that can visualize cells that made specific cell-cell contact.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-71474-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7468259PMC
September 2020

Comparison of 30-day readmission and emergency department revisit rates among homeless patients at teaching versus non-teaching hospitals.

Soc Sci Med 2020 10 14;263:113283. Epub 2020 Aug 14.

Division of General Internal Medicine and Health Services Research, UCLA David Geffen School of Medicine, Los Angeles, CA, USA; Department of Health Policy and Management, UCLA Fielding School of Public Health, Los Angeles, CA, USA; UCLA Center for Health Policy Research, Los Angeles, CA, USA.

Providing quality healthcare for homeless patients is a major public health challenge, and some hospitals may be better at treating homeless patients than others. However, whether the quality of care that homeless patients receive differs by the teaching status of hospitals remains unclear. Using statewide databases that include all hospital admissions and emergency department (ED) visits in four states (Florida, Massachusetts, Maryland, and New York) in 2014, we compared 30-day readmission and ED revisit rates for homeless and non-homeless patients discharged from teaching hospitals versus non-teaching hospitals, after adjusting for patient and hospital characteristics. Among 3,438,538 patients (median age [IQR]: 63 [49-77] years) analyzed, 132,025 (4%) were homeless patients. Overall, homeless patients had a higher readmission rate (28.3% vs. 17.7%; average marginal effects [AME], 10.5%; 95% confidence interval [CI], 8.2%-12.9%; p < 0.001) and a higher ED revisit rate (37.6% vs. 23.9%; AME, 13.7%; 95%CI, 10.9%-16.6%; p < 0.001) than non-homeless patients. Patients from teaching hospitals had similar readmission rate (18.2% vs. 18.3%; AME, -0.1%; 95%CI, -0.8%-0.5%; p = 0.69) and slightly lower ED revisit rate than those from non-teaching hospitals (24.1% vs. 25.2%; AME, -1.1%; 95%CI, -1.9% to -0.3%; p < 0.01). When we focus on joint effects of homelessness and hospital teaching status, we found that homeless patients treated at teaching hospitals had lower rates of 30-day readmission (AME, -5.8%; 95%CI, -9.7% to -1.8%; p < 0.01) and ED revisit (AME, -9.3%; 95%CI, -13.1% to -5.5%; p < 0.001) compared to those treated at non-teaching hospitals. For non-homeless patients, in contrast, we found no evidence that rates of hospital readmission (AME, 0%, 95%CI, -0.1%-0.1%; p = 0.94) or ED revisit (AME, -0.9%; 95%CI, -1.7% to -0.1%; p = 0.02) differ between teaching and non-teaching hospitals. These findings suggest the healthcare settings in which homeless patients receive care have important implications for their patient outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.socscimed.2020.113283DOI Listing
October 2020

Place of death associated with types of long-term care services near the end-of-life for home-dwelling older people in Japan: a pooled cross-sectional study.

BMC Palliat Care 2020 Aug 9;19(1):121. Epub 2020 Aug 9.

Health Services Research and Development Center, University of Tsukuba, 1-1-1 Tenno-dai, Tsukuba, Ibaraki, 305-8575, Japan.

Background: Many older people wish to die at home. However, there is still a huge gap between the place where older adults wish to die and the place where they, in fact, do die. We aimed to assess the association between each type of long-term care (LTC) services that home-dwelling older individuals utilized at their end of life and place of death.

Methods: A pooled cross-sectional study at the point of death was used for the analysis. Participants included beneficiaries of long-term care insurance in Japan, aged 65 years and above, who passed away between January 2008 and December 2013, excluding those who died due to external factors and those who were using residential services at their time of death. We conducted a multivariate Poisson regression analysis with robust standard errors adjusting for potential confounders and examined the association between the use of each type of LTC service for home-dwelling recipients, including in-home services, day services, and short-stay services, with the interaction terms being time of death (exposure) and home death (outcome). We calculated the adjusted probability of home deaths for each combination pattern of LTC services for home-dwelling recipients using standard marginalization.

Results: We analyzed 2,035,657 beneficiaries. The use of in-home services, day services, and short-stay services were associated with an increased probability of home deaths; the incident rate ratio (IRR) was 13.40 (with a 95% confidence interval (CI): 13.23-13.57) for in-home services, the IRR was 6.32 (6.19-6.45) for day services, and the IRR was 1.25 (1.16-1.34) for short-stay services. Those who used day or short-stay services with in-home services exhibited a higher probability of home deaths than those who used only day or short-stay services.

Conclusions: We demonstrated that home-dwelling older persons who used LTC services near end-of-life had a higher probability of home deaths as compared to those who did not. Our findings can clarify the importance of providing and integrating such services to support care recipients who wish to die at home as well as for the benefit of their informal caregivers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12904-020-00622-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7416406PMC
August 2020

Hospital Readmission and Emergency Department Revisits of Homeless Patients Treated at Homeless-Serving Hospitals in the USA: Observational Study.

J Gen Intern Med 2020 09 14;35(9):2560-2568. Epub 2020 Jul 14.

Division of General Internal Medicine and Health Services Research, UCLA David Geffen School of Medicine, Los Angeles, CA, USA.

Background: As the U.S. homeless population grows, so has the challenge of providing effective care to homeless individuals. Understanding hospitals that achieve better outcomes after hospital discharge for homeless patients has important implications for making our health system more sustainable and equitable.

Objective: To determine whether homeless patients experience higher rates of readmissions and emergency department (ED) visits after hospital discharge than non-homeless patients, and whether the homeless patients exhibit lower rates of readmissions and ED visits after hospital discharge when they were admitted to hospitals experienced with the treatment of the homeless patients ("homeless-serving" hospitals-defined as hospitals in the top decile of the proportion of homeless patients).

Design: A population-based longitudinal study, using the data including all hospital admissions and ED visits in FL, MA, MD, and NY in 2014.

Participants: Participants were 3,527,383 patients (median age [IQR]: 63 [49-77] years; 1,876,466 [53%] women; 134,755 [4%] homeless patients) discharged from 474 hospitals.

Main Measures: Risk-adjusted rates of 30-day all-cause readmissions and ED visits after hospital discharge.

Key Results: After adjusting for potential confounders, homeless patients had higher rates of readmissions (adjusted rate, 27.3% vs. 17.5%; adjusted odds ratio [aOR], 1.93; 95% CI, 1.69-2.21; p < 0.001) and ED visits after hospital discharge (37.1% vs. 23.6%; aOR, 1.98; 95% CI, 1.74-2.25; p < 0.001) compared with non-homeless patients. Homeless patients treated at homeless-serving hospitals exhibited lower rates of readmissions (23.9% vs. 33.4%; p < 0.001) and ED visits (31.4% vs. 45.4%; p < 0.001) after hospital discharge than homeless patients treated at non-homeless-serving hospitals.

Conclusions: Homeless patients were more likely to be readmitted or return to ED within 30 days after hospital discharge, especially when they were treated at hospitals that treat a small proportion of homeless patients. These findings suggest that homeless patients may receive better discharge planning and care coordination when treated at hospitals experienced with caring for homeless people.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11606-020-06029-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7459070PMC
September 2020

Effect of reduced formal care availability on formal/informal care patterns and caregiver health: a quasi-experimental study using the Japanese long-term care insurance reform.

BMC Geriatr 2020 06 12;20(1):207. Epub 2020 Jun 12.

Health Services Development and Research Center, University of Tsukuba, 1-1-1 Tennodai, Tsukuba-shi, Ibaraki, 3058577, Japan.

Background: It is unclear how formal long-term care (LTC) availability affects formal /informal caregiving patterns and caregiver health. We tested the impact of reduced formal LTC availability on formal LTC service use, intensity of informal caregiving, and caregiver health.

Methods: Using a representative, repeated cross-sectional sample of Japanese caregivers providing care to co-resident family members from 2001 to 2016, we applied a difference-in-differences approach by observing caregivers before and after the major reform of the public Japanese LTC insurance (LTCI) in 2006. The reform reduced coverage benefits for non-institutionalized older persons with low care needs, but not for those with high care needs. We analyzed 12,764 caregivers aged ≥30 years (mean age 64.3 ± 11.8 years, 73.5% women) and measured indicators of formal LTC use, hours of informal caregiving, and caregiver self-reported health outcomes after propensity score matching to balance caregivers' background characteristics.

Results: We found the 2006 LTCI reform relatively reduced the use of formal LTC services and relatively increased the percentage of experiencing long hours of informal caregiving (> 3 h per day) among the caregivers for seniors with low care needs compared to those for seniors with high care needs. The effects of the LTCI reform for the caregivers for seniors with low care needs were 2.2 percentage point higher on caregivers' experiencing poor self-rated health (95% confidence interval [CI]: 0.7-3.7; p = 0.01), 2.7 percentage point higher on experiencing symptoms of a depressive state (95%CI: 0.5-4.8; p = 0.03), and 4.7 percentage point higher on experiencing symptoms of musculoskeletal diseases (95%CI, 3.6-5.7; p < 0.001), compared to those for seniors with high care needs.

Conclusions: Reduced formal care availability under the Japanese LTCI reform increased hours of informal caregiving corresponding to reduced use of formal LTC and deteriorated multiple dimensions of caregiver health. Our findings may highlight the importance of enhancing the availability of formal LTC services for caregiver health.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12877-020-01588-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7291452PMC
June 2020

A discrete neuronal circuit induces a hibernation-like state in rodents.

Nature 2020 07 11;583(7814):109-114. Epub 2020 Jun 11.

Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.

Hibernating mammals actively lower their body temperature to reduce energy expenditure when facing food scarcity. This ability to induce a hypometabolic state has evoked great interest owing to its potential medical benefits. Here we show that a hypothalamic neuronal circuit in rodents induces a long-lasting hypothermic and hypometabolic state similar to hibernation. In this state, although body temperature and levels of oxygen consumption are kept very low, the ability to regulate metabolism still remains functional, as in hibernation. There was no obvious damage to tissues and organs or abnormalities in behaviour after recovery from this state. Our findings could enable the development of a method to induce a hibernation-like state, which would have potential applications in non-hibernating mammalian species including humans.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41586-020-2163-6DOI Listing
July 2020

Lessons from Influenza Outbreaks for Potential Impact of COVID-19 Outbreak on Hospitalizations, Ventilator Use, and Mortality Among Homeless Persons in New York State.

J Gen Intern Med 2020 09 4;35(9):2781-2783. Epub 2020 Jun 4.

Division of General Internal Medicine and Health Services Research, UCLA David Geffen School of Medicine, Los Angeles, CA, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11606-020-05876-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7272140PMC
September 2020

Visualizing and Modulating Mitophagy for Therapeutic Studies of Neurodegeneration.

Cell 2020 05 20;181(5):1176-1187.e16. Epub 2020 May 20.

Laboratory for Cell Function Dynamics, RIKEN Center for Brain Science, 2-1 Hirosawa, Wako-City, Saitama 351-0198, Japan; Biotechnological Optics Research Team, Center for Advanced Photonics, RIKEN, 2-1 Hirosawa, Wako-City, Saitama 351-0198, Japan. Electronic address:

Dysfunctional mitochondria accumulate in many human diseases. Accordingly, mitophagy, which removes these mitochondria through lysosomal degradation, is attracting broad attention. Due to uncertainties in the operational principles of conventional mitophagy probes, however, the specificity and quantitativeness of their readouts are disputable. Thorough investigation of the behaviors and fates of fluorescent proteins inside and outside lysosomes enabled us to develop an indicator for mitophagy, mito-SRAI. Through strict control of its mitochondrial targeting, we were able to monitor mitophagy in fixed biological samples more reproducibly than before. Large-scale image-based high-throughput screening led to the discovery of a hit compound that induces selective mitophagy of damaged mitochondria. In a mouse model of Parkinsons disease, we found that dopaminergic neurons selectively failed to execute mitophagy that promoted their survival within lesions. These results show that mito-SRAI is an essential tool for quantitative studies of mitochondrial quality control.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cell.2020.04.025DOI Listing
May 2020

Physician Distribution by Specialty and Practice Setting: Findings in Japan in 2000, 2010 and 2016.

Tohoku J Exp Med 2020 05;251(1):1-8

Department of Public Health, Graduate School of Medicine, The University of Tokyo.

As the medical demand is projected to increase along with the population aging in Japan, the geographical distribution of physicians is a significant concern for society and policymakers. To implement effective measures on geographical physician distribution, this study aimed to describe and compare the distribution of physicians by specialty in 2000, 2010 and 2016 in Japan, and examine whether practice setting was associated with distribution. To quantify the geographical physician distribution by specialty, we calculated the Gini coefficients of physicians working at clinics or hospitals in 2000, 2010, and 2016. We used the basic geographic unit for medical care planning in Japan, a secondary medical area, as the study unit. To show the association between the geographical distribution of physicians in each specialty and their practice setting, we categorized specialties into two groups by the proportion of physicians in that specialty working in hospitals, and showed aggregated Lorenz curves for each category. The overall geographical distribution of physicians appeared to improve during the study period, but varied by specialty. Those in specialties, where at least 90% of physicians work in hospitals such as anesthesiologists and radiologists, were more clustered, as shown by the Lorenz curves and the Gini coefficients. Similar distributional differences were also found even when we excluded physicians working in clinics, meaning that the distributional variation could be explained by other factors than the distribution of hospitals. These results suggest that the nature of practice in each specialty strongly affects the geographical distribution of specialists.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1620/tjem.251.1DOI Listing
May 2020

Development of near-infrared firefly luciferin analogue reacted with wild-type and mutant luciferases.

Chirality 2020 07 4;32(7):922-931. Epub 2020 May 4.

Department of Engineering Science, Graduate School of Informatics and Engineering,, The University of Electro-Communications, Chofu, Japan.

Interestingly, only the D-form of firefly luciferin produces light by luciferin-luciferase (L-L) reaction. Certain firefly luciferin analogues with modified structures maintain bioluminescence (BL) activity; however, all L-form luciferin analogues show no BL activity. To this date, our group has developed luciferin analogues with moderate BL activity that produce light of various wavelengths. For in vivo bioluminescence imaging, one of the important factors for detection sensitivity is tissue permeability of the number of photons emitted by L-L reaction, and the wavelengths of light in the near-infrared (NIR) range (700-900 nm) are most appropriate for the purpose. Some NIR luciferin analogues by us had performance for in vivo experiments to make it possible to detect photons from deep target tissues in mice with high sensitivity, whereas only a few of them can produce NIR light by the L-L reactions with wild-type luciferase and/or mutant luciferase. Based on the structure-activity relationships, we designed and synthesized here a luciferin analogue with the 5-allyl-6-dimethylamino-2-naphthylethenyl moiety. This analogue exhibited NIR BL emissions with wild-type luciferase (λ = 705 nm) and mutant luciferase AlaLuc (λ = 655 nm).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/chir.23236DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7383472PMC
July 2020

Space Radiation Biology for "Living in Space".

Biomed Res Int 2020 8;2020:4703286. Epub 2020 Apr 8.

Gunma University Heavy Ion Medical Center, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan.

Space travel has advanced significantly over the last six decades with astronauts spending up to 6 months at the International Space Station. Nonetheless, the living environment while in outer space is extremely challenging to astronauts. In particular, exposure to space radiation represents a serious potential long-term threat to the health of astronauts because the amount of radiation exposure accumulates during their time in space. Therefore, health risks associated with exposure to space radiation are an important topic in space travel, and characterizing space radiation in detail is essential for improving the safety of space missions. In the first part of this review, we provide an overview of the space radiation environment and briefly present current and future endeavors that monitor different space radiation environments. We then present research evaluating adverse biological effects caused by exposure to various space radiation environments and how these can be reduced. We especially consider the deleterious effects on cellular DNA and how cells activate DNA repair mechanisms. The latest technologies being developed, e.g., a fluorescent ubiquitination-based cell cycle indicator, to measure real-time cell cycle progression and DNA damage caused by exposure to ultraviolet radiation are presented. Progress in examining the combined effects of microgravity and radiation to animals and plants are summarized, and our current understanding of the relationship between psychological stress and radiation is presented. Finally, we provide details about protective agents and the study of organisms that are highly resistant to radiation and how their biological mechanisms may aid developing novel technologies that alleviate biological damage caused by radiation. Future research that furthers our understanding of the effects of space radiation on human health will facilitate risk-mitigating strategies to enable long-term space and planetary exploration.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2020/4703286DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7168699PMC
January 2021

Relative Income Deprivation and All-Cause Mortality in Japan: Do Life Priorities Matter?

Ann Behav Med 2020 09;54(9):665-679

Department of Social and Behavioral Sciences, Harvard T. H. Chan School of Public Health, Boston, MA, USA.

Background/purpose: Relative deprivation (RD) is proposed to affect health through psychosocial stress stemming from upward social comparisons. This study hypothesized that prioritizing values, such as social engagement and personal growth (as opposed to prioritizing work), would inoculate against the toxic effects of upward social comparisons.

Methods: Prospective data of 9,533 subjects (4,475 men and 5,058 women) participating in the Komo-Ise study answering a baseline questionnaire in 1993 and a follow-up survey in 2000 were analyzed. Associations between RD-using Yitzhaki Index (YI) and Income Rank (IR)-and mortality were evaluated using Cox proportional-hazard regression models. At follow-up, people were also asked about what they prioritized in life: work, social engagement, or personal growth.

Results: 1,168 deaths (761 men and 407 women) occurred during follow-up (to the end of 2011). Controlling for sociodemographic factors, the hazard ratio (HR) for mortality was 1.22 (95% confidence interval [CI] = 1.08-1.38) per a standard deviation (SD) increase in YI and 1.18 (95% CI = 1.03-1.35) per an SD decrease in IR. Life priorities (LP) were not statistically significantly associated with mortality. In women, the interaction between LP and YI was statistically significant. In fully adjusted models, women who endorsed only work as very important in their lives had a 2.66 (95% CI = 1.23-5.77) times higher HR for mortality per SD increase in YI compared to women who valued social engagement/personal growth. An interaction between LP and RD was not found in men.

Conclusions: Increased relative income deprivation was associated with a higher risk of all-cause mortality independently of absolute income. Focusing on social engagement/personal growth (as opposed to work) appears to inoculate women against the toxic effects of relative deprivation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/abm/kaaa010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7459183PMC
September 2020